TPPP3 Overexpression Suppresses Nasopharyngeal Carcinoma Progression and Promotes Immune Microenvironment Remodeling Through HSPA8 Association

Abstract

Simple Summary Nasopharyngeal carcinoma is a head and neck cancer linked to Epstein–Barr virus infection. Some patients respond well to immunotherapy, but many do not, and the reasons for this difference remain unclear. In this study, we investigated a protein called TPPP3, which is present at low levels in nasopharyngeal carcinoma cells. We found that increasing TPPP3 in cancer cells slowed tumor growth in both cell models and mice with humanized immune systems. It also attracted more cancer-fighting immune cells, including T cells and dendritic cells, into the tumor. We further discovered that TPPP3 physically interacts with another protein, HSPA8, which helps maintain protein balance within cells. When we blocked HSPA8 with a drug, the tumor-suppressing effects of TPPP3 became even stronger. These findings suggest that targeting the interaction between TPPP3 and HSPA8 could offer a new approach to improving immunotherapy outcomes for patients with nasopharyngeal carcinoma.